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Multiplex Genome Engineering Using CRISPR/Cas Systems

Multiplex Genome Engineering Using CRISPR/Cas Systems | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Le Cong, F. Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini, Feng Zhang

"Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology."

 http://bit.ly/VVv3yb

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Synthetic Biologists Make First Steps Toward Biological Computers

Synthetic Biologists Make First Steps Toward Biological Computers | SynBioFromLeukipposInstitute | Scoop.it
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by
Joann Fan 

"Synthetic biology is a field that began more than a decade ago when James Collins, a synthetic biologist at Boston University in Massechusetts developed a genetic 'toggle switch.' He activated the switch in Escherichia coli cells, which are harmless bacteria found in the intestinal tract, and in 2009 he and several others developed a synthetic gene network that could count various user-defined inputs.

This week, Timothy Lu, who worked with Collins in 2009, published a paper in this week's Nature Biotechnology describing the process of altering cells into being able to respond to the 16 binary logic functions (boolean operators such as true, false, and, not, or, etc.). This research takes biology another step closer to electrical engineering, allowing scientists to, someday, encode even more complex computations into cells."We wanted to show you can assemble a bunch of simple parts in a very easy fashion to give you many types of logical functions," Lu, who led the research, told Nature. He and his team developed 16 plasmids (circular strings of DNA) - one for each of the boolean functions - and inserted them into the E. coli cells.Each plasmid type has a promoter and terminator DNA sequence, which regulates gene transcription (the first step in gene expression, where a segment of DNA is copied onto RNA), as well as an 'output gene' that triggers the production of a green glowing protein.You can think of the plasmid as the switch in a logic circuitboard. When certain conditions are fulfilled, it will either transcribe or fail to transcribe the output gene (in this case, green flourescence). "An electric 'AND' gate," which Nature uses as its example, "only gives a positive output when voltage is applied to both inputs." In an electric 'OR' gate, voltage can be applied to either gate, but not both to produce a positive output.In the genetic version of an 'AND' gate, two terminator sequences between the start and the finish must be neutralized by specific kinds of signal enzymes called recombinase, which can snip and rearrange the controller genes, before the output will be transcribed. For example in the picture below, a 'Recombinase 1' and 'Recombinase 2' would have to alter their respective 'Terminator' genes before the 'Output' gene will activate.

Most importantly, the changes triggered by signal compounds would be permanent. Lu's team found that the altered plasmids will be passed down through at least 90 cell generations, which could give a biologist valuable insight on when something may have happened in a cell's ancestry.Lu said that in theory, manufacturers could grow cell cultures that can produce drugs when triggered to, or grow cultures whose production can be halted with the introduction of signal compounds."


http://bit.ly/WKVOnx


original ref:

*Synthetic circuits integrating logic and memory in living cells* byPiro Siuti, John Yazbek & Timothy K Lu "Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications." http://bit.ly/123ToU3
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A Novel Approach for the Construction of Industrial Microorganisms

A Novel Approach for the Construction of Industrial Microorganisms | SynBioFromLeukipposInstitute | Scoop.it
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by
Daslav Hranueli, Antonio Starcevic, Jurica Zucko, Juan Diego Rojas, Janko Diminic, Damir Baranasic, Ranko Gacesa, Gabriel Padilla, Paul F. Long and John Cullum

"The recent achievement of synthesising a functioning bacterial chromosome marks a coming of age for engineering living organisms. In the future this should allow the construction of novel organisms to help solve the problems facing the human race, including health care, food, energy and environmental protection. In this minireview, the current state of the field is described and the role of synthetic biology in biotechnology in the short and medium term is discussed. It is particularly aimed at the needs of food technologists, nutritionists and other biotechnologists, who might not be aware of the potential significance of synthetic biology to the research and development in their fields. The potential of synthetic biology to produce interesting new polyketide compounds is discussed in detail."

http://bit.ly/14UvJUM

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Redirector: Designing Cell Factories by Reconstructing the Metabolic Objective

Redirector: Designing Cell Factories by Reconstructing the Metabolic Objective | SynBioFromLeukipposInstitute | Scoop.it
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*Redirector*: *Designing Cell Factories by Reconstructing the Metabolic Objective* 

by

Graham Rockwell, Nicholas J. Guido, George M. Church

"A deeper understanding of biological processes, along with methods in synthetic biology, is driving the frontier of metabolic engineering. In particular, a better representation of cell metabolism will enable the engineering of bacterial strains that can act as factories for valuable biochemical products, from medicines to biofuels. Models which predict the behavior of these complex biological systems enable better engineering design as well as a more comprehensive understanding of fundamental biological principles. Here we develop a new method, called Redirector, for modeling metabolic alterations, and their relationship to cell growth. This method optimizes genetic engineering changes to achieve metabolite production using a new representation of the metabolic impact of genetic manipulation, which is more biologically realistic than existing models. We discover proven and novel engineering targets to improve fatty acid production, correctly predicting how different combinations of genes build upon one another. This work demonstrates that Redirector is a powerful method for designing cell factories and improving our understanding of metabolic systems."


http://bit.ly/X5L2Yi

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Systems metabolic engineering in an industrial setting

Systems metabolic engineering in an industrial setting | SynBioFromLeukipposInstitute | Scoop.it
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*

by
Sagt CM.

"Systems metabolic engineering is based on systems biology, synthetic biology, and evolutionary engineering and is now also applied in industry. Industrial use of systems metabolic engineering focuses on strain and process optimization. Since ambitious yields, titers, productivities, and low costs are key in an industrial setting, the use of effective and robust methods in systems metabolic engineering is becoming very important. Major improvements in the field of proteomics and metabolomics have been crucial in the development of genome-wide approaches in strain and process development. This is accompanied by a rapid increase in DNA sequencing and synthesis capacity. These developments enable the use of systems metabolic engineering in an industrial setting. Industrial systems metabolic engineering can be defined as the combined use of genome-wide genomics, transcriptomics, proteomics, and metabolomics to modify strains or processes. This approach has become very common since the technology for generating large data sets of all levels of the cellular processes has developed quite fast into robust, reliable, and affordable methods. The main challenge and scope of this mini review is how to translate these large data sets in relevant biological leads which can be tested for strain or process improvements. Experimental setup, heterogeneity of the culture, and sample pretreatment are important issues which are easily underrated. In addition, the process of structuring, filtering, and visualization of data is important, but also, the availability of a genetic toolbox and equipment for medium/high-throughput fermentation is a key success factor. For an efficient bioprocess, all the different components in this process have to work together. Therefore, mutual tuning of these components is an important strategy."

http://1.usa.gov/Vdlbgo

fig 
Cellular metabolism can be optimized for industrial use.http://en.wikipedia.org/wiki/Metabolic_engineering ;
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Bio hacking at @genspace Synthetic biology on saturdays

Bio hacking at @genspace  Synthetic biology on saturdays | SynBioFromLeukipposInstitute | Scoop.it
WP_20130209_005.jpg (Bio hacking at @genspace Synthetic biology on saturdays http://t.co/EjQFz1wc)
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Synthetic circuits integrating logic and memory in living cells

Synthetic circuits integrating logic and memory in living cells | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Piro Siuti,John Yazbek& Timothy K Lu

"Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications."

http://bit.ly/123ToU3

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Genetic engineering – the next generation

Genetic engineering – the next generation | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:
*Genetic engineering* – *the next generation*  By Oliver Adams "n the past genetic engineering has arguably just been a cut and paste job, take a gene or two from one organism put it into another and observe. Whilst this technology has served us incredibly well, producing everything from insulin to glowing mice (not to mention a little controversy), we are on the precipice of change. Increasing DNA sequencing and artificial DNA synthesis efficiencies are giving way to an emerging interdisciplinary field, with a radically new perspective – Synthetic Biology. Whilst difficult to neatly define, Synthetic Biology broadly encompasses much more ambitious genetic manipulations of life than attempted in the past. It does this using approaches which involve the application of engineering and computing principles to cellular function. The former refers to the standardisation of biological parts, so called BioBricks. These are publicly available DNA sequences coding for predetermined, supposedly compatible, functional cellular components (e.g. a specific enzyme). The growing pool of BioBricks represents a repository of interchangeable functional modules. These can then be combined by the user to form new metabolic networks, of defined function, in their “chassis” of choice (usually E.coli). The potential applications of this form of Synthetic Biology are wide ranging, as best exemplified by the annual iGEM competitors. iGEM, the international genetically engineered machines competition, is an undergraduate Synthetic Biology competition (peculiarly Oxford doesn’t have a team) which has been running since 2004. One of iGEMs main aims is to promote advancements in Synthetic Biology by challenging teams to engineer organisms with novel functions, by creating new or using available BioBricks. Such endeavours have produced the aptly named E.chromi and BactoBlood, both derived from E.coli. The former is a biosensor derivative which changes to a variety of colours in response to local concentrations of a given inducer. The latter is a potential blood transfusion substitute, in which E.coli has been engineered to carry oxygen (i.e. produce haemoglobin) in the bloodstream whilst not inducing any complications (e.g. blood poisoning)......" http://bit.ly/Y3k81c
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The EyeWire Games Begin Feb 13

The EyeWire Games Begin Feb 13 | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

How can we use the collaborative power found on the internet to solve scientific problems? Gamification of science is a potential solution.

*The EyeWire Games begin on Feb 13th*


"The EyeWire Games are 7 days of team competition between Facebook, Reddit, Twitter, Google+ and Team X (Veterans). The team that maps the most 3D neuron volume in one week receives the ultimate reward: neuron naming rights. Your team is the social network where you discovered EyeWire."


http://blog.eyewire.org/the-eyewire-games-begin-feb-13/

"EyeWire is an online, Citizen science, human-based computation game about tracing neurons in the retina. The game is a project developed by MIT and the Max Planck Institute for Medical Research, led by Dr. Sebastian Seung

The goals of the EyeWire project are to identify specific cell types within the known broad classes of retinal cells, and to map the connections between neurons in the retina, which will help to determine how vision works.[2][3] EyeWire is part of a larger effort called WiredDifferently, whose goal is to show that the uniqueness of a person lies in the pattern of connections between their neurons, or their connectome.[4][5]The first immediate goal is to reconstruct the three-dimensional shapes of retinal neurons from two-dimensional images.[6] The second goal is to identify the synapses to determine what the connections between the mapped neurons are. The final goal is to relate the connectivity with the known activity of the neurons." 

http://en.wikipedia.org/wiki/EyeWire

This game is an interesting contribution to the solution of an important question for contemporary science:


*How to use and benefit from collaborative intelligence found in the Cloud for research*? "An important trend is that many people participate in social networks. These platforms provide the potential option of planetary scale connectivity among researchers and the ability to organize research projects solely in the cloud. The availability of high-performing computing resources, such as online cloud computing and storage platforms, grid-enabled platforms and communication channels, provides the context necessary for important innovations in modern science.  As a consequence, social networks provide a context for the enormous amount of data. This dramatically expands our combined brain power, because a group of people is more likely to solve a complex problem (Nielsen).  Moreover, collaboration becomes independent of our physical location, reducing the transaction costs to zero (Treuille).  This new kind of research collaboration has different names such as crowdsourcing or crowdfunding, depending on the type of collaboration. A good example to that effect is the FoldIT and EteRNA games (Cooper, Treuille)." http://bit.ly/TtuNOP


See also these interesting references about *collaborative science*:

Solve for X: Adrien Treuille on collaborative sciencehttp://bit.ly/ziK0YJ  and Michael Nielsen, Reinventing Discovery, TheNew Era of Networked Science, Princeton University Press 2012.“Michael Nielsen argues that we are living at the dawn of the mostdramatic change in science in more than 300 years. This is beingdriven by powerful new cognitive tools, enabled by the internet, whichare greatly accelerating scientific discovery....this is the firstbook about something much more fundamental how the internet istransforming the nature of our collective intelligence and how weunderstand the world” (cover text)http://amzn.to/H74pZS
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‘Can simple biological systems be built from standardized interchangeable parts?’ Negotiating biology and engineering in a synthetic biology competition

‘Can simple biological systems be built from standardized interchangeable parts?’ Negotiating biology and engineering in a synthetic biology competition | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Emma Frowa & Jane Calverta 

"Synthetic biology represents a recent attempt to bring engineering principles and practices to working with biology. In practice, the nature of the relationship between engineering and biology in synthetic biology is a subject of ongoing debate. The disciplines of biology and engineering are typically seen to involve different ways of knowing and doing, and to embody different assumptions and objectives. Tensions between these approaches are playing out as the field of synthetic biology is being established. Here, we study negotiations between engineering and biology through the International Genetically Engineered Machine (iGEM) competition. This undergraduate competition has been important in launching and bootstrapping the field of synthetic biology, and serves as a test-bed for the engineering approach. We show how a number of issues that iGEM teams must grapple with – including standardization, design, intellectual property, and the imagination of the social – involve the negotiation of engineering, biology, and other disciplines (including computer science), in ways more complex than the engineering rhetoric of synthetic biology implies. We suggest that a new moral economy for synthetic biology is being created, in which epistemic and institutional values, conventions, and practices are being negotiated and (re)defined."

http://bit.ly/12BC8FS

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Transferring a synthetic gene circuit from yeast to mammalian cells

Transferring a synthetic gene circuit from yeast to mammalian cells | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Dmitry Nevozhay,Tomasz Zal& Gábor Balázsi

"The emerging field of synthetic biology builds gene circuits for scientific, industrial and therapeutic needs. Adaptability of synthetic gene circuits across different organisms could enable a synthetic biology pipeline, where circuits are designed in silico, characterized in microbes and reimplemented in mammalian settings for practical usage. However, the processes affecting gene circuit adaptability have not been systematically investigated. Here we construct a mammalian version of a negative feedback-based 'linearizer' gene circuit previously developed in yeast. The first naïve mammalian prototype was non-functional, but a computational model suggested that we could recover function by improving gene expression and protein localization. After rationally developing and combining new parts as the model suggested, we regained function and could tune target gene expression in human cells linearly and precisely as in yeast. The steps we have taken should be generally relevant for transferring any gene circuit from yeast into mammalian cells."

 http://bit.ly/VJwiuS

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MSBW: Mammalian Synthetic Biology Workshop

MSBW: Mammalian Synthetic Biology Workshop | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

 

Venue: Stata Center, MIT, Cambridge, Massachusetts, USA Date: Saturday morning, May 11 to Sunday noon May 12, 2013 Recognizing the fast emergence and potential significance of this field, the aim of this workshop is to bring together practitioners of mammalian synthetic biology together with experts from other relevant fields. The general goals of the workshop are to nucleate the nascent mammalian synthetic biology community, reach out to experts from other fields that can benefit from and contribute to this field, and define the important challenges and future directions. The workshop format will provide a forum for exposition of the latest developments in the field and discussions of how experts from other fields can benefit from and contribute to mammalian synthetic biology. Perhaps more importantly, the workshop will also include breakout sessions that will identify the main challenges and opportunities. Findings from the breakout sessions will be assembled into a written report that will be distributed to all workshop participants and to relevant government and funding agencies. The agenda on Saturday will include several 30 minute talks about mammalian synthetic biology tools and capabilities, talks about industrial and clinical applications, and two sets of breakout sessions. The first set of breakout sessions will focus on the technology, including large scale DNA assembly and integrationtranscriptional regulationsensors and actuatorsnon-transcriptional regulation.The second set of breakout sessions will focus on potential disease and scientific inquiry applications, including cancerstem cell and tissue engineeringvaccination and infectious diseasediabetes and metabolic diseasesdrug screening.The emphasis in these sessions will be on understanding and evaluating the transformative opportunities for synthetic biology in these areas. Sunday morning will include two talks and then reports from all breakout sessions. The workshop will end Sunday at noon. Organizing Committee: Ron Weiss, MIT, ChairPamela A. Silver, Harvard, Co-ChairNoubar Afeyan, Flagship VenturesJon Chesnut, Life TechnologiesGeorge M. Church, HarvardJames J. Collins, BULeonard Katz, SynBERCChristina D. Smolke, Stanford 
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New Tool for Genome Surgery

New Tool for Genome Surgery | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
John van der Oost

"Gene therapy is the holy grail of human medicine. Many diseases are caused by a defective gene, sometimes with a mutation as subtle as a single-nucleotide variation. Before restoration of such a mutation in a patient's genome can take place, the target nucleotide sequence has to be cleaved at a single position, out of 3 billion possibilities. This degree of precise surgery requires an enzyme with highly selective target recognition. Successful editing of eukaryotic genomes has been accomplished with DNA nucleases designed to bear a unique site that binds to a specific DNA sequence. A major drawback of these protein-guided systems to "engineer" genomes, however, is that each new target sequence requires laboriously adjusting the specificity of the nuclease's DNA binding site. On pages 819 and 823 of this issue, Cong et al. (1) and Mali et al. (2) describe efficient genome editing in human cells based on an RNA-guided system."
http://bit.ly/XSpKf0

Referring to:
*Multiplex Genome Engineering Using CRISPR/Cas Systems*
by
Le Cong et al.
http://bit.ly/VVv3yb

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Eriko Takano - 4th New Phytologist Workshop

Eriko Takano - 4th New Phytologist Workshop | SynBioFromLeukipposInstitute | Scoop.it
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*Synthetic biology of antibiotic production*

Talk by 
Eriko Takano 

"Speaker abstract

Streptomyces bacteria are well known for their ability to produce an immense diversity of secondary metabolites, including many antibiotics. The underlying biosynthetic machinery is a particularly interesting target for synthetic biology, due to its inherent modularity at multiple levels1,2. A treasure trove of antibiotic biosynthesis gene clusters has been identified by genome sequencing, typically 20–50 per genome3,4. We can use synthetic biology to re-engineer the bacterial genomes to awaken this multitude of cryptic antibiotic clusters. We have already demonstrated the potential of this strategy by awakening the cryptic/orphan CPK gene cluster5, which produces a novel antibacterial compound. Generalizing this approach using standardized molecular modules will become a central tool for discovering new bioactive compounds, ranging from anti-cancer drugs to antibiotics6."


http://bit.ly/14UxvFm

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A Whole-Cell Model As a Tool to Guide Synthetic Biology

A Whole-Cell Model As a Tool to Guide Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
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by
Jayodita Sanghvi, Jonathan R. Karr, Derek Macklin, Miriam Gutschow, Jared Jacobs, Benjamin Bolival, John Glass, Nacyra Assad-Garcia and Markus W. Covert

 

Abstarct (SBE’s 6th International Conference on Bioengineering and Nanotechnology)

"Researchers have spent years uncovering the molecular mechanisms of the numerous processes in a cell, from metabolism to cell division. Still, an integrated comprehension of this knowledge remains a challenge. We have attempted to collate the community's understanding and have built the first comprehensive computational model of a single living cell. This model of the simplest known self-replicating organism, Mycoplasma genitalium, describes all of the known gene functions and molecular interactions. It includes data from over 900 publications and over 1900 parameters. The model incorporates the cross talk between 28 cellular processes including metabolism, transcription, translation, replication, and cell division. Each process was first independently modeled using different mathematical representations, such as linear optimization, ordinary differential equations, probabilistic binding, and geometry, that were best fit for the individual cellular processes. Then, the 28 processes were integrated together at a one-second timestep. The whole-cell model has been validated and benchmarked against existing physiological data, and we have performed additional experiments to further validate the model. The resulting simulations predict cell behavior in response to genomic and environmental perturbations as well as phenotypes that lead to questions that have never before been addressed. The model is able to predict kinetic rates, new gene annotations, chromosomal occupancy, energy usage, new forms of cell cycle regulation, and much more.

 We hope that that this whole-cell model and expansions on this model will accelerate biological discovery and bioengineering by serving as tools to guide synthetic biology. Further, in combination with the recent de novo synthesis and transplantation of Mycoplasma genomes to produce a synthetic cell (Gibson et al., 2008; Gibson et al., 2010), whole-cell models raise the possibility of computer-aided rational design of novel microorganisms."


http://bit.ly/12EhiB6

Fig
http://en.wikipedia.org/wiki/Mycoplasma_genitalium

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How to turn living cells into computers

How to turn living cells into computers | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Roland Pease

"Synthetic biologists have developed DNA modules that perform logic operations in living cells. These ‘genetic circuits’ could be used to track key moments in a cell’s life or, at the flick of a chemical switch, change a cell’s fate, the researchers say. Their results are described this week in Nature Biotechnology1.

 Synthetic biology seeks to bring concepts from electronic engineering to cell biology, treating gene functions as components in a circuit. To that end, researchers at the Massachusetts Institute of Technology (MIT) in Cambridge have devised a set of simple genetic modules that respond to inputs much like the Boolean logic gates used in computers. “These developments will more readily enable one to create programmable cells with decision-making capabilities for a variety of applications,” says James Collins, a synthetic biologist at Boston University in Massachusetts who was not involved in the study...."


http://bit.ly/VSSUOR

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Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

*Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators*

by
Su Ryon Shin , Sung Mi Jung , Momen Zalabany , Keekyoung Kim , Pinar Zorlutuna , Sang bok Kim , Mehdi Nikkhah , Masoud Khabiry , Mohamed Azize , Jing Kong , Kai-tak Wan , Tomas Palacios , Mehmet R Dokmeci , Hojae Bae , Xiaowu (Shirley) Tang , and Ali Khademhosseini

"We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT) incorporated photocrosslinkable gelatin methacrylate (GelMA) hydrogel. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework is the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity."

http://bit.ly/Y5x7O4


see also by the same last author

*Carbon Nanotube Reinforced Hybrid Microgels as Scaffold Materials for Cell Encapsulation*
http://bit.ly/Y5xQ1U


is also source of the fig

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Cell circuits remember their history

Cell circuits remember their history | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:


by
Anne Trafton

"MIT engineers have created genetic circuits in bacterial cells that not only perform logic functions, but also remember the results, which are encoded in the cell’s DNA and passed on for dozens of generations.

 The circuits, described in the Feb. 10 online edition of Nature Biotechnology, could be used as long-term environmental sensors, efficient controls for biomanufacturing, or to program stem cells to differentiate into other cell types. “Almost all of the previous work in synthetic biology that we’re aware of has either focused on logic components or on memory modules that just encode memory. We think complex computation will involve combining both logic and memory, and that’s why we built this particular framework to do so,” says Timothy Lu, an MIT assistant professor of electrical engineering and computer science and biological engineering and senior author of the Nature Biotechnology paper. Lead author of the paper is MIT postdoc Piro Siuti. Undergraduate John Yazbek is also an author.  More than logic Synthetic biologists use interchangeable genetic parts to design circuits that perform a specific function, such as detecting a chemical in the environment. In that type of circuit, the target chemical would generate a specific response, such as production of green fluorescent protein (GFP).   Circuits can also be designed for any type of Boolean logic function, such as AND gates and OR gates. Using those kinds of gates, circuits can detect multiple inputs. In most of the previously engineered cellular logic circuits, the end product is generated only as long as the original stimuli are present: Once they disappear, the circuit shuts off until another stimulus comes along.  Lu and his colleagues set out to design a circuit that would be irreversibly altered by the original stimulus, creating a permanent memory of the event. To do this, they drew on memory circuits that Lu and colleagues designed in 2009. Those circuits depend on enzymes known as recombinases, which can cut out stretches of DNA, flip them, or insert them. Sequential activation of those enzymes allows the circuits to count events happening inside a cell. Lu designed the new circuits so that the memory function is built into the logic gate itself. With a typical cellular AND gate, the two necessary inputs activate proteins that together turn on expression of an output gene. However, in the new circuits, the inputs stably alter regions of DNA that control GFP production. These regions, known as promoters, recruit the cellular proteins responsible for transcribing the GFP gene into messenger RNA, which then directs protein assembly. For example, in one circuit described in the paper, two DNA sequences called terminators are interposed between the promoter and the output gene (GFP, in this case). Each of these terminators inhibits the transcription of the output gene and can be flipped by a different recombinase enzyme, making the terminator inactive.  Each of the circuit’s two inputs turns on production of one of the recombinase enzymes needed to flip a terminator. In the absence of either input, GFP production is blocked. If both are present, both terminators are flipped, resulting in their inactivation and subsequent production of GFP.  Once the DNA terminator sequences are flipped, they can’t return to their original state — the memory of the logic gate activation is permanently stored in the DNA sequence. The sequence also gets passed on for at least 90 generations. Scientists wanting to read the cell’s history can either measure its GFP output, which will stay on continuously, or if the cell has died, they can retrieve the memory by sequencing its DNA. Using this design strategy, the researchers can create all two-input logic gates and implement sequential logic systems. “It’s really easy to swap things in and out,” says Lu, who is also a member of MIT’s Synthetic Biology Center. “If you start off with a standard parts library, you can use a one-step reaction to assemble any kind of function that you want.” Long-term memory Such circuits could also be used to create a type of circuit known as a digital-to-analog converter. This kind of circuit takes digital inputs — for example, the presence or absence of single chemicals — and converts them to an analog output, which can be a range of values, such as continuous levels of gene expression.  For example, if the cell has two circuits, each of which expresses GFP at different levels when they are activated by their specific input, those inputs can produce four different analog output levels. Moreover, by measuring how much GFP is produced, the researchers can figure out which of the inputs were present. That type of circuit could offer better control over the production of cells that generate biofuels, drugs or other useful compounds. Instead of creating circuits that are always on, or using promoters that need continuous inputs to control their output levels, scientists could transiently program the circuit to produce at a certain level. The cells and their progeny would always remember that level, without needing any more information.  Used as environmental sensors, such circuits could also provide very precise long-term memory. “You could have different digital signals you wanted to sense, and just have one analog output that summarizes everything that was happening inside,” Lu says. This platform could also allow scientists to more accurately control the fate of stem cells as they develop into other cell types. Lu is now working on engineering cells to follow sequential development steps, depending on what kinds of inputs they receive from the environment.  Michael Jewett, an assistant professor of chemical and biological engineering at Northwestern University, says the new design represents a “huge advancement in DNA-encoded memory storage.” “I anticipate that the innovations reported here will help to inspire larger synthetic biology efforts that push the limits of engineered biological systems,” says Jewett, who was not involved in the research."http://bit.ly/Y3KzUJ


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Synthetic biology, the bioeconomy, and a societal quandary

Synthetic biology, the bioeconomy, and a societal quandary | SynBioFromLeukipposInstitute | Scoop.it
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Jim C. Philp , Rachael J. Ritchie*, Jacqueline E.M. Allan

"Opinions on what synthetic biology actually is range from a natural extension of genetic engineering to a new manufacturing paradigm. It offers, for the first time in the life sciences, rational design and engineering standardisation. It could address problems across a broad spectrum of human concerns, including energy and food security, and health of growing and aging populations. It also offers great scope for public resistance to its introduction to daily life...."

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Homegrown labware made with 3D printer

Homegrown labware made with 3D printer | SynBioFromLeukipposInstitute | Scoop.it
'Smart' containers can be customized to drive chemical reactions.
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A comprehensive approach to zinc-finger recombinase customization enables genomic targeting in human cells

A comprehensive approach to zinc-finger recombinase customization enables genomic targeting in human cells | SynBioFromLeukipposInstitute | Scoop.it
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Gaj T, Mercer AC, Sirk SJ, Smith HL, Barbas CF

"Zinc-finger recombinases (ZFRs) represent a potentially powerful class of tools for targeted genetic engineering. These chimeric enzymes are composed of an activated catalytic domain derived from the resolvase/invertase family of serine recombinases and a custom-designed zinc-finger DNA-binding domain. The use of ZFRs, however, has been restricted by sequence requirements imposed by the recombinase catalytic domain. Here, we combine substrate specificity analysis and directed evolution to develop a diverse collection of Gin recombinase catalytic domains capable of recognizing an estimated 3.77 × 10(7) unique DNA sequences. We show that ZFRs assembled from these engineered catalytic domains recombine user-defined DNA targets with high specificity, and that designed ZFRs integrate DNA into targeted endogenous loci in human cells. This study demonstrates the feasibility of generating customized ZFRs and the potential of ZFR technology for a diverse range of applications, including genome engineering, synthetic biology and gene therapy."

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Bacterial cultures: ontologies of bacteria and engineering expertise at the nexus of synthetic biology and water services

Bacterial cultures: ontologies of bacteria and engineering expertise at the nexus of synthetic biology and water services | SynBioFromLeukipposInstitute | Scoop.it
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Andrew S. Balmera & Susan Molyneux-Hodgson

"In this paper we report on ethnographic work developed over two years, working as social scientists within a project on synthetic biology (SB), which aimed to use engineered bacteria as solutions to water industry problems. We were asked to help solve the ‘barrier to innovation’ by our engineering colleagues who believed that industrial and public ignorance would block their innovations. Instead of orienting around ‘ignorance’ we chose to explore the different ontologies of bacteria that were adopted in the various practices of the many sites involved in the project. We describe our observations in microbiological laboratories and compare them to a waste water treatment facility. Engineers in the lab understand bacteria as controllable but also vulnerable, thus their ability to manipulate and protect bacteria becomes important in their claims to expertise. In contrast, engineers in the water facility understand bacteria as dangerous, but they become skilled in protecting their bodies, make sense of their relation to bacteria through immunological narratives and claim expertise through an olfactory epistemology. Overall, we conclude that the ontologies of ‘engineer’ and ‘bacteria’ are interrelated through context-specific practices. Finally, we argue that this account is instructive for current policy and engagement discussions around SB."

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Synthetic Biology Webinars

Synthetic Biology Webinars | SynBioFromLeukipposInstitute | Scoop.it
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Synthetic Biology Webinar

"Learning Made Easier with Synthetic Biology Webinars
Inquire, Understand, and Break Through to Discovery

At Life Technologies, we believe synthetic biology will change the way we create energy, produce food, optimize industrial processing, and detect, prevent, and cure diseases—improving the human condition and the world around us. We’re committed to offering unparalleled technology and solutions to the research community. With our platform of synthetic biology products, we intend to understand and answer some of life’s most challenging questions. Through design and engineering, our scientists enable researchers to study, alter, create, and re-create highly complex pathways, DNA sequences, genes, and natural biological systems. In the synthetic biology webinar series from Life Technologies, our scientists cover the different challenges that synthetic biology researchers encounter and address the solutions available to help them achieve their next breakthroughs.

Stay at the forefront of synthetic biology breakthroughs, register for a live webinar, or view our library of past webinars at your leisure. New webinars are added monthly, so subscribe now and be among the first to learn about the latest advances in synthetic biology research."
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A Genetic Device Performs DNA Diagnosis

A Genetic Device Performs DNA Diagnosis | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

via +Deeptak Verma 

*A biological device made of DNA inserted into a bacterial cell works like a tiny diagnostic computer*

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Weizmann Institute of Science

"Scientists hope that one day in the distant future, miniature, medically-savvy computers will roam our bodies, detecting early-stage diseases and treating them on the spot by releasing a suitable drug, without any outside help. To make this vision a reality, computers must be sufficiently small to fit into body cells. Moreover, they must be able to “talk” to various cellular systems. These challenges can be best addressed by creating computers based on biological molecules such as DNA or proteins. The idea is far from outrageous; after all, biological organisms are capable of receiving and processing information, and of responding accordingly, in a way that resembles a computer.

 Researchers at the Weizmann Institute of Science have recently made an important step in this direction: They have succeeded in creating a genetic device that operates independently in bacterial cells. The device has been programmed to identify certain parameters and mount an appropriate response. The device searches for transcription factors – proteins that control the expression of genes in the cell. A malfunction of these molecules can disrupt gene expression. In cancer cells, for example, the transcription factors regulating cell growth and division do not function properly, leading to increased cell division and the formation of a tumor. The device, composed of a DNA sequence inserted into a bacterium, performs a “roll call” of transcription factors. If the results match preprogrammed parameters, it responds by creating a protein that emits a green light – supplying a visible sign of a “positive” diagnosis. In follow-up research, the scientists – Prof. Ehud Shapiro and Dr. Tom Ran of the Biological Chemistry and Computer Science and Applied Mathematics Departments – plan to replace the light-emitting protein with one that will affect the cell’s fate, for example, a protein that can cause the cell to commit suicide. In this manner, the device will cause only “positively” diagnosed cells to self-destruct. In the present study, published in Nature's Scientific Reports, the researchers first created a device that functioned like what is known in computing as a NOR logical gate: It was programmed to check for the presence of two transcription factors and respond by emitting a green light only if both were missing. When the scientists inserted the device into four types of genetically engineered bacteria – those making both transcription factors, those making none of the transcription factors, and two types making one of the transcription factors each – only the appropriate bacteria shone green. Next, the research team – which also included graduate students Yehonatan Douek and Lilach Milo – created more complex genetic devices, corresponding to additional logical gates. Following the success of the study in bacterial cells, the researchers are planning to test ways of recruiting such bacteria as an efficient system to be conveniently inserted into the human body for medical purposes (which shouldn’t be a problem; recent research reveals there are already 10 times more bacterial cells in the human body than human cells). Yet another research goal is to operate a similar system inside human cells, which are much more complex than bacteria."

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